title: Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy.
abstract: Aging is associated with an increased incidence of heart failure, but the existence of an age-related cardiomyopathy remains controversial. Differences in strain, age and technique of measuring cardiac function differ between experiments, confounding the interpretation of these studies. Additionally, the structural and genetic profile at the onset of heart failure has not been extensively studied. We therefore performed serial echocardiography, which allows repeated assessment of left ventricular (LV) function, on a cohort of the same mice every 3 months as they aged and demonstrated that LV systolic dysfunction becomes apparent at 18 months of age. These aging animals had left ventricular hypertrophy and fibrosis, but did not have inducible ventricular tachyarrhythmias. Gene expression profiling of left ventricular tissue demonstrated 40 differentially expressed probesets and 36 differentially expressed gene ontology terms, largely related to inflammation and immunity. At this early stage of cardiac dysfunction, we observed increased cardiomyocyte expression of the pro-apoptotic activated caspase-3, but no actual increase in apoptosis. The aging hearts also have higher levels of anti-apoptotic and autophagic factors, which may have rendered protection from apoptosis. In conclusion, we describe the functional, structural and genetic changes in murine hearts as they first develop cardiomyopathy of aging.
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94143, United States. aboyle@medicine.ucsf.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Henry
authors.initials: H
authors.lastname: Shih
authors.forename: Joy
authors.initials: J
authors.lastname: Hwang
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Brian
authors.initials: B
authors.lastname: Lee
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Kwon
authors.forename: Kristine
authors.initials: K
authors.lastname: Jun
authors.forename: Daiwei
authors.initials: D
authors.lastname: Zheng
authors.forename: Rich
authors.initials: R
authors.lastname: Sievers
authors.forename: Franca
authors.initials: F
authors.lastname: Angeli
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Randall
authors.initials: R
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004452:Echocardiography; D005355:Fibrosis; D020869:Gene Expression Profiling; D006321:Heart / Q000502:physiology*; D006984:Hypertrophy; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000473:pathology; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology